The present invention relates to a virucidal disinfectant having broad-range activity, the use of said disinfectant for the hygienic disinfection of animate and inanimate surfaces as well as for killing viruses, bacteria and fungi.
Further, the invention relates to a disinfection method and to a product containing a disinfectant.
In recent years, disinfectants have gained importance. Of particular importance is the use of disinfectants in field such as hospitals, medical practices, old-age homes, emergency wards, but also in factories which are not related with medical aid, such as food-producing factories, in the pharmaceutical branch and in further branches in which working under clean room conditions is necessary. Particularly important in these fields is the disinfection of hands, because the latter are often responsible for the communication of all kinds of pathogens.
The disinfection of hands is an established method for preventing the transmission of infections. For this purpose, alcohol-based products for rubbing are used today according to the prior art. This principle has been known for about 30 years. The preparations employed are usually based on the active substances ethanol, propane-1-ol, propane-2-ol and mixtures of the mentioned alcohols.
With the known commercially available preparations, which have an alcohol content of 60% and more, it is possible to reduce the transient germ flora of the hands efficiently within 30 seconds.
The mentioned alcohols and their mixtures as well as many commercially available preparations are able to inactivate enveloped viruses. However, if a comprehensive antiviral effectiveness is required, the alcohols as well as the preparations known to the skilled person have a number of drawbacks. Thus, it is known that ethanol is effective against enveloped and non-enveloped viruses only in high concentrations. In contrast, propane-1-ol and propane-2-ol are only selectively effective; they are ineffective against most non-enveloped viruses, e.g., against the highly resistant picornaviruses, which include polioviruses and hepatitis A virus.
In the past, several attempts were made for enhancing the effectiveness of alcoholic rubbing preparations against viruses. As a result, some preparations are known for which virucidal effectiveness is stated.
U.S. published patent application No. 2004/0146479 A1 describes compositions for hand disinfection. An exemplary composition contains 55% (w/v) of ethanol (70% v/v), 0.1% (w/v) of phosphoric acid, 6% (w/v) of polyethylene glycol (400), 2% (w/v) of polyethylene glycol (4000), 0.50% (w/v) of propylene glycol and 0.35% (w/v) of benzyl alcohol.
The European Unexamined Patent Application EP-A2-0 556 546 describe agents which are characterized by containing at least 60% of at least one alcohol as well as at least one Lewis acid. As Lewis acids, salts of aluminum or zinc are mentioned, the chlorohydrates and chlorides being particularly pointed out. The products are supposed to have effectiveness against poliovirus type 1 strain Mahoney. Chlorides are known to have corrosive properties, which is also referred to as chloride-induced pitting. The disclosure of German Offenlegungsschrift DE-A1-4205828 is to be evaluated in similar terms.
The European Unexamined Patent Application EP-A2-0 176 720 describes agents which contain at least 70% methanol and/or ethanol, from 1 to 10% glycerol and from 0.5 to 5% castor oil and are suitable for inactivating non-enveloped viruses. The demonstration has been effected exclusively with the wild type poliovirus type 1 Mahoney.
The European Unexamined Patent Application EP-A2-0 251 303 discloses a virucidal agent which contains at least 70% ethanol and a short-chain acid. The agent can additionally contain glycerol and castor oil. The application properties of such products have proven non-optimum due to the sticky skin feeling after the application.
The German Offenlegungsschrift DE-A1-4221743 describes agents which contain a lower alcohol as well as the salt of a lower carboxylic acid. Products formulated on the basis of this teaching have proven non-effective against papovaviruses, even if the time of action was extended to 10 minutes.
A commercially available preparation contains 32.251 g of propan-1-ol, 20.985 g of propan-2-ol, 4.2 g of 20% chlorohexidine digluconate solution, 1-tetradecanol, Macrogol 4000, cetearyl octanoate, patent blue V, perfumes and purified water. According to the manufacturer, this preparation is effective against vaccinia viruses, rotaviruses, hepatitis B viruses, hepatitis C viruses and human immunodeficiency viruses (HIV).
A preparation obtainable in the Federal Republic of Germany contains 95% ethanol as a basic active ingredient as well as denaturing agents and skin-care substances. In the list of the Robert Koch Institute (RKI), the product is rated as effective against viruses. According to the manufacturer, its required time of action is 2 minutes. The required time of action against papovaviruses and adenoviruses determines the effectiveness. Against polioviruses, the preparation is effective within 60 seconds. The preparation is insufficiently effective against parvoviruses. According to the manufacturer, the flash point of the preparation is 0° C. The storage and shipping of such a preparation are correspondingly demanding.
The German Patent Specification DE-C1-4424325 and the European Unexamined Patent Application EP-A1-0 692 192 describe an alcoholic disinfectant formulation having a content of ethanol and/or methanol of at least 80 percent by weight, which is characterized by containing butanone. The formulation may contain chlorohexidine or benzalkonium chloride as remanent active ingredients. The formulation may contain an alkylene glycol, namely triethylene glycol or glycerol, as well as an ester of a long-chain fatty acid as care substances. The disinfectant formulation is claimed for the inactivation of non-enveloped viruses, especially polioviruses.
The German Offenlegungsschrift DE-A1-19962353 describes a hepatitis A virucidal agent which contains one or more alcohols and up to 0.5% of a chlorine-containing or chlorine-releasing agent. The agent may further contain up to 10% of antimicrobial acids, such as undecylenic acid, citric acid, p-hydroxybenzoic acid, sorbic acid, salicylic acid. A commercially available preparation contains 90% ethanol, 0.20% chlorohexidine gluconate and further additives. This preparation is evidently based on the German Patent Specification DE-C1-4424325 and/or the German Offenlegungsschrift DE-A1-19962353. The commercially available preparation has a low flash point, which is stated by the manufacturer to be 15° C. An effectiveness of this preparation against papovaviruses is not known.
The Published International Patent Application WO-A1 97/35475 discloses a product having a flash point of above 21° C. which contains lower alcohols and synergists. As synergists, diols, especially propylene glycol, butylene glycol and their mixtures, are employed. The product may contain a physiologically acceptable organic acid. A commercial product which is based on this patent specification contains 54.1% ethanol, 10% 1-propanol, 5.90% propane-1,2-diol and 5.7% butane-1,3-diol. For short-term application, the product seems to be suitable for hand disinfection. However, when used continuously, the high content of non-volatile diols proves to be disturbing, because these diols remain on the hands as a residue and can cause an uncomfortable skin feeling. Especially for application for hand disinfection in surgery, preparations according to WO-A1-97/35475 have limited suitability.
The European Unexamined Patent Application EP-A1-0 848 907 claims a spray disinfectant which contains from 30 to 70% of ethanol, an amine component and a terpene hydrocarbon. Using it, preparations having activity against polioviruses can be formulated. However, due to their composition, products of this type can be employed only for the disinfection of inanimate surfaces.
The German Offenlegungsschrift DE-A1-10237227 describes an alcoholic hand and skin disinfectant with ascorbic acid and/or its degradation products, which is supposed to have improved activity against poliovirus type 1 strain Mahoney and adenovirus strain adenoid 6. One of its degradation products is oxalic acid, which not physiologically acceptable.
Peracids are known to exhibit activity against bacteria and viruses, so that it appears obvious to employ peracids also for the disinfection of hands. In this connection, the RKI list states a preparation based on diluted aqueous peracetic acid, which has not been rated “effective against viruses”, however.
The German Offenlegungsschrift DE-A1-19724102 describes agents for rapid disinfection or decontamination comprising a content of physiologically acceptable peracids. It is not known whether this product is also effective against viruses. Irrespective thereof, it is difficult to handle, and the stability of the ready-to-use solutions to be employed is limited.
The German Offenlegungsschrift DE-A1-10106444 claims agents for virucidal hand disinfection which are prepared from components A and B, wherein component A consists of from 50 to 80% of a liquid aliphatic alcohol or mixtures of liquid aliphatic alcohols, and component B comprises a 20% to 30% solution of glycerol monoperacetate diacetate and/or glycerol monoperacetate acetate and/or glycol monoperacetate acetate and urea. Components A and B must be combined in a dosing and mixing device. Components A and B are supposed to be stable, but the mixture of components A and B is not storage-stable over an extended period of time. In addition, the mixing of the components requires a higher logistic expenditure, for example, in order to guard against the risk of confusion of the components. Also, the dosing and mixing device is to be designed to avoid the premature consumption of one of the components at any rate.
Inorganic acids mostly have a limited effectiveness against viruses. In the Handbuch der Viruswirksamen Desinfektion (ISBN 3-540-67532-9), published by the Springer Verlag, Berlin, Heidelberg, New York, in 2002, the authors point out on page 79 that some viruses which have to pass the stomach in the course of their infection path are fairly resistant against acids. The authors stress the point that phosphoric acid is still ineffective against poliovirus in a concentration as high as 3%.
In the past, the Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM) declared preparations for instrument disinfection as virucidal in their list if an activity against the poliovirus type 1 strain Mahoney could be detected. However, a general virucidal property cannot be concluded from the activity against poliovirus alone. On the other hand, it is neither possible nor reasonable to intend to test the activity against all known viruses individually. Currently, this is not possible for mere methodic reasons, because no possibility of in vitro growth has been found as yet for a number of viruses in spite of the advanced technical progress.
Therefore, when virucidal property is established, it has been found appropriate to establish the effectiveness by means of selected critical model viruses in order to conclude to a general virucidal property on the basis of such results. This approach is supported by the Directions of the German Federal Public Health Administration and the Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten of 1982.
These Directions have been updated by the Comment, issued in 2004, of the Working Group Virucidal Property of the Robert Koch Institute (RKI) and the Specialist Panel “Virus disinfection” of the Deutsche Gesellschaft zur Bekämpfung der Viruskrankheiten (DVV) and the Disinfectant Commission of the Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM).
In this Comment, the testing and declaration of effectiveness of disinfectants against viruses is newly settled in the form of an RKI Recommendation. This RKI Recommendation has appeared in the technical journal Bundesgesundheitsblatt—Gesundheitsforschung—Gesundheitsschutz 2004, 47, pp. 62-66. In the following text, this Recommendation is shortly referred to as “RKI Virucidal Property Recommendation”.
According to this RKI Virucidal Property Recommendation, preparations claiming virucidal effectiveness are tested in the Federal Republic of Germany against the following model viruses: adenovirus type 5 (strain Adenoid 75), papovavirus [simian virus 40 (SV40), strain 777], poliovirus (polio vaccination strain type I, strain LSc-2ab), vaccinia virus (strain Elstree). A preparation is considered effective against the respective test virus if a reduction of the virus titer of at least 4 logarithmic steps is achieved in a quantitative suspension experiment.
In the testing for virucidal property, 8 parts of product, 1 part of virus suspension and 1 part of load substance or water are mixed. Due to methodic conditions, this results in an 80% concentration of the test preparation. The test preparations are examined without a load, with a load of 0.2% bovine albumin and with a load of 10% fetal calf serum. Only a preparation which achieves a reduction of the virus titer of at least 4 logarithmic steps under all test conditions meets the conditions of the RKI with respect to antiviral effectiveness. In the European Testing Standard EN 14476, which describes the quantitative suspension experiment for virucidal property in human medicine, it is noted under item 1 that a disinfectant or antiseptic agent which is used neat must be tested in 80% concentration.
If a test preparation fails to reach the required effectiveness against the test virus, it has become established that the manufacturer concentrates his product by dispensing with part of the water normally contained in his formulation, and a thus especially processed preparation is again tested at a higher concentration. Thus, in the literature, statements about test preparations can be found in which, although antiviral effectiveness within 1 to 2 minutes is stated, the concentration of the test preparations is documented as being, for example, 90%, 94% or 100%. Strictly speaking, this is a deviation from the standard test conditions, and such preparations are thus not really to be rated as virucidal in accordance with the RKI Virucidal Property Recommendation and the European Testing Standard EN 14476. In addition, the objective mutual comparability of the preparations is rendered more difficult.
If the Directions of the Federal Public Health Administration and the Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten of 1982 are compared with the current RKI Virucidal Property Recommendation, it strikes that individual test viruses have been changed for methodic reasons. Thus, the wild type poliovirus type 1, strain Mahoney, was used formerly instead of the vaccination strain type I, strain LSc-2ab. A similar situation holds for the adenovirus, in which case the strain Adenoid 6 was used formerly. The changes in the viral strains yielded interesting results. A slightly modified product based on the active ingredients 78.2% of 96% ethanol and 10% of 2-propanol, which had achieved effectiveness against the poliovirus type 1 strain Mahoney within 2 minutes, proved to be insufficiently effective against the poliovirus vaccination strain type I, strain LSc-2ab. Therefore, it is to be doubted whether the results established in the past relating to the effectiveness of preparations towards the poliovirus type 1 strain Mahoney can be generally transferred to the poliovirus vaccination strain type I, strain LSc-2ab.
Another problem is seen in the practice of hand disinfection. As a rule, medical institutions have several preparations on store nowadays: one product for routine disinfection and another preparation to be applied especially for exposure to unknown viruses. The logistic problems resulting therefrom and the high demands on personnel training are a challenge which is not to be underestimated.
It is noted that today there is still a need for improved disinfectants, especially hand disinfectants, with virucidal effectiveness, especially for those which have a broad-range activity and are suitable both for routine use and for exposure to unknown viruses.